{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:44:59Z","timestamp":1773027899461,"version":"3.50.1"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["RSP2024R885"],"award-info":[{"award-number":["RSP2024R885"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Tuberculosis (TB) remains a critical global health challenge, with the emergence of drug-resistant strains heightening concerns. The development of effective drugs targeting both wild-type (WT) and mutant <jats:italic>Escherichia coli<\/jats:italic> RNA polymerase \u03b2 subunit (RpoB) is crucial for global TB control, aiming to alleviate TB incidence, mortality, and transmission. This study employs molecular docking and ADMET analyses to screen echinoderm metabolites for their potential inhibition of <jats:italic>Escherichia coli<\/jats:italic> RNA polymerase, focusing on wild-type and mutant RpoB variants associated with TB drug resistance. The evaluation of docking results using the glide gscore led to the selection of the top 10 compounds for each protein receptor. Notably, CMNPD2176 demonstrated the highest binding affinity against wild-type RpoB, CMNPD13873 against RpoB D516V mutant, CMNPD2177 against RpoB H526Y mutant, and CMNPD11620 against RpoB S531L mutant. ADMET screening confirmed the therapeutic potential of these selected compounds. Additionally, MM-GBSA binding free energy calculations and molecular dynamics simulations provided further support for the docking investigations. While the results suggest these compounds could be viable for tuberculosis treatment, it is crucial to note that further in-vitro research is essential for the transition from prospective inhibitors to clinical drugs.<\/jats:p>","DOI":"10.1371\/journal.pone.0304587","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T17:24:38Z","timestamp":1725038678000},"page":"e0304587","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of echinoderm metabolites as potential inhibitors targeting wild-type and mutant forms of Escherichia coli RNA polymerase (RpoB) for tuberculosis treatment"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1391-6973","authenticated-orcid":true,"given":"Fatimah M.","family":"Alsulais","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8340-4395","authenticated-orcid":true,"given":"Bayan A.","family":"Alhaidhal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramzi A.","family":"Mothana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2565-6573","authenticated-orcid":true,"given":"Abdullah R.","family":"Alanzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,8,30]]},"reference":[{"issue":"3","key":"pone.0304587.ref001","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.ijtb.2020.02.005","article-title":"A systemic review on tuberculosis","volume":"67","author":"A. Natarajan","year":"2020","journal-title":"Indian Journal of Tuberculosis"},{"issue":"43","key":"pone.0304587.ref002","article-title":"The diagnosis and treatment of tuberculosis","volume":"116","author":"I. Su\u00e1rez","year":"2019","journal-title":"Deutsches Aerzteblatt International"},{"issue":"3","key":"pone.0304587.ref003","doi-asserted-by":"crossref","first-page":"2201322","DOI":"10.1002\/smtd.202201322","article-title":"Highly Sensitive Detection of Complicated Mutations of Drug Resistance in Mycobacterium tuberculosis Using a Simple, Accurate, Rapid, and Low\u2010Cost Tailored\u2010Design Competitive Wild\u2010Type Blocking Assay.","volume":"7","author":"M. Yan","year":"2023","journal-title":"Small Methods"},{"key":"pone.0304587.ref004","doi-asserted-by":"crossref","first-page":"4119","DOI":"10.2147\/IDR.S333433","article-title":"rpoB mutations and effects on rifampin resistance in Mycobacterium tuberculosis.","author":"M. 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Sinha","year":"2020","journal-title":"BMC microbiology"},{"issue":"2","key":"pone.0304587.ref007","doi-asserted-by":"crossref","first-page":"e03168","DOI":"10.1128\/mbio.03168-22","article-title":"Mutations in rpoB that confer rifampicin resistance can alter levels of peptidoglycan precursors and affect \u03b2-lactam susceptibility.","volume":"14","author":"Y. Patel","year":"2023","journal-title":"Mbio"},{"issue":"13","key":"pone.0304587.ref008","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.3390\/molecules25133011","article-title":"The war against tuberculosis: A review of natural compounds and their derivatives","volume":"25","author":"M. Maiolini","year":"2020","journal-title":"Molecules"},{"key":"pone.0304587.ref009","first-page":"656419","volume":"12","author":"M. Ozturk","year":"2021","journal-title":"Evaluation of Berberine as an Adjunct to TB Treatment. 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Salo-Ahen","year":"2020","journal-title":"Processes"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0304587","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T17:25:19Z","timestamp":1725038719000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0304587"}},"subtitle":[],"editor":[{"given":"Ahmed A.","family":"Al-Karmalawy","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,8,30]]},"references-count":44,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0304587","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,30]]}}}